Biodegradable controlled antibiotic release devices for osteomyelitis: optimization of release properties

J Pharm Pharmacol. 1994 Sep;46(9):718-24. doi: 10.1111/j.2042-7158.1994.tb03890.x.

Abstract

Controlled antibiotic release films, melt-extruded cylinders, and suspension-extruded/coated cylinders were manufactured from biodegradable poly(D,L-lactide) (PDLLA) and poly(D,L-lactide-co-epsilon-caprolactone). These devices have potential application in the treatment of osteomyelitis. The in-vitro release properties of the devices were examined with drug loadings varying from 16 to 50%. Gentamicin sulphate films and melt-extruded gentamicin/PDLLA cylinders demonstrated a large initial burst and incomplete release. The films and melt-extruded cylinders made from poly(D,L-lactide-co-epsilon-caprolactone), low mol. wt poly(D,L-lactide), and a mixture of D,L-lactic acid oligomer and high mol. wt poly(D,L-lactide), did not remain intact during the entire release period. While this is undesirable, these materials do have the advantage of not requiring a processing temperature of greater than 110 degrees C. Antibiotic release from high mol. wt PDLLA-coated gentamicin/PDLLA cylinders, with 40 and 50% loading, was very rapid. The antibiotic could only diffuse out through the open ends of the cylinder. Coated gentamicin sulphate cylinders with 20 and 30% drug loading gave the most promising properties in terms of a small initial burst, and a gradual and sustained release. The release rate and duration from the coated cylinders could be adjusted by cutting the cylinder into different lengths; the time required for 90% of the entrapped gentamicin to be released into water from 30% loaded PDLLA-coated cylinders 0.2, 0.4, 0.7 and 1 cm in length was 1000, 1700, 2300, and 2800 h, respectively. This offers a convenient method to adjust the release to meet the specific antibiotic requirement of different patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials* / chemistry
  • Biodegradation, Environmental
  • Cefazolin / pharmacokinetics
  • Delayed-Action Preparations*
  • Gentamicins / chemistry
  • Gentamicins / pharmacokinetics*
  • Humans
  • Lactates / chemistry
  • Lactic Acid*
  • Osteomyelitis / drug therapy*
  • Osteomyelitis / metabolism
  • Penicillin G / pharmacokinetics
  • Polyesters / chemistry
  • Polymers / chemistry

Substances

  • Biocompatible Materials
  • Delayed-Action Preparations
  • Gentamicins
  • Lactates
  • Polyesters
  • Polymers
  • Lactic Acid
  • poly(lactide)
  • lactide-caprolactone copolymer
  • Cefazolin
  • Penicillin G